hCAS/CSE1L regulates RAD51 distribution and focus formation for homologous recombinational repair
hCAS/CSE1L regulates RAD51 distribution and focus formation for homologous recombinational repair
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DOI：
10.1111/gtc.12262
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发表时间：
2015-09-01
期刊：
影响因子：
2.1
通讯作者：
Tashiro, Satoshi
中科院分区：
文献类型：
--
作者：
Okimoto, Satoshi;Sun, Jiying;Tashiro, Satoshi
同源重组修复（Homologous recombinational repair， HR）是DNA双链断裂的主要修复系统之一。RAD51是HR中的关键分子，DNA损伤诱导后细胞核内RAD51浓度升高。然而，调控RAD51在细胞内分布的机制尚不清楚。在这里，我们发现hCAS/CSE1L在人类细胞中与RAD51结合。我们发现hCAS/CSE1L在正常情况下负调控RAD51的核蛋白水平。hCAS/CSE1L也需要抑制DNA损伤诱导的RAD51的病灶形成。此外，我们发现hCAS/CSE1L在HR活性和染色体稳定性的调控中发挥作用。这些发现表明，hCAS/CSE1L通过直接与RAD51相互作用来控制HR活性。
Homologous recombinational repair (HR) is one of the major repair systems for DNA double-strand breaks. RAD51 is a key molecule in HR, and the RAD51 concentration in the cell nucleus increases after DNA damage induction. However, the mechanism that regulates the intracellular distribution of RAD51 is still unclear. Here, we show that hCAS/CSE1L associates with RAD51 in human cells. We found that hCAS/CSE1L negatively regulates the nuclear protein level of RAD51 under normal conditions. hCAS/CSE1L is also required to repress the DNA damage-induced focus formation of RAD51. Moreover, we show that hCAS/CSE1L plays roles in the regulation of the HR activity and in chromosome stability. These findings suggest that hCAS/CSE1L is responsible for controlling the HR activity by directly interacting with RAD51.